Prevention of AIDS-related opportunistic infections (OI's) offers a major opportunity to improve both the quality and length of life of patients suffering from this devastating disease. Clinical studies have demonstrated the efficacy of prophylaxis in preventing the major 01's associated with AIDS. The Cost of prevention is high, however, and may add substantially to the estimated $5 billion per year currently spent on AIDS care in the United States. Previous research on cost-effective approaches to HIV care has focused on specific strategies for prophylaxis against individual 01's. It may be more appropriate, however, for physicians and policy makers to treat the epidemic as a family of interdependent diseases, assessing the costs and effects of integrated prophylactic strategies, in order to determine the impact of prevention regimens on HIV-related expenditures. Pneumocystis carinii pneumonia (PCP), Mycobacterium avium Complex (MAC), cytomegalovirus (CMV) and fungal infections are the most common OI's in AIDS patients. Large randomized trials of prophylaxis, under the auspices of the national AIDS Clinical Trials Group (ACTG), are in the process of assessing the efficacy of preventive therapies. These include: aerosolized pentamidine, trimethoprim-sulfamethoxazole, and dapsone for PCP prophylaxis; rifabutin and/or clarithromycin for MAC prophylaxis; valaciclovir to prevent CMV; and clotrimazole troches and oral fluconazole for the prevention of fungal infections. Little research has been conducted, however, to evaluate the downstream economic consequences of widespread implementation of these interventions. In order to evaluate the alternative strategies for the prevention of OI's in people with AIDS, we propose to embed new clinical and cost data from recent randomized trials and observational cohorts into the structure of a comprehensive, decision-analytic, cost-effectiveness model. We will employ a state-transition (or Markov) framework to simulate the natural history of HIV and its major associated OI's and to assess the costs, benefits, and cost-effectiveness of prophylaxis. To capture both the complexity and the rapid rate of technological change that characterize the clinical management of patients with HIV infection, the model we propose is dynamic in its nature and flexible in its structure: it can be expanded to incorporate data on other covariates, such as the effects of a future vaccine or prophylaxis against other OI's. Such timely and essential information will be vital to clinicians and policy makers for the development of rational approaches to the management of the HlV epidemic.